PD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer

Human Vγ2Vδ2 (also termed Vγ9Vδ2) T cells play important roles in microbial and tumor immunity by monitoring foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis. Accumulation of isoprenoid metabolites after bisphosphonate treatment allows Vγ2Vδ2 T cells to recognize and kil...

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Autores principales:	Mohanad H. Nada, Hong Wang, Auter J. Hussein, Yoshimasa Tanaka, Craig T. Morita
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	adoptive immunotherapy programed cell death 1 receptor prostatic neoplasms inhibitory t cell receptors combined modality therapy human γδ t cells vγ2vδ2 t cells Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/44888b298b5348eaa2d0982d33df0a10
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spelling	oai:doaj.org-article:44888b298b5348eaa2d0982d33df0a102021-11-04T15:00:45ZPD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer2162-402X10.1080/2162402X.2021.1989789https://doaj.org/article/44888b298b5348eaa2d0982d33df0a102021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/2162402X.2021.1989789https://doaj.org/toc/2162-402XHuman Vγ2Vδ2 (also termed Vγ9Vδ2) T cells play important roles in microbial and tumor immunity by monitoring foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis. Accumulation of isoprenoid metabolites after bisphosphonate treatment allows Vγ2Vδ2 T cells to recognize and kill tumors independently of their MHC expression or burden of non-synonymous mutations. Clinical trials with more than 400 patients show that adoptive immunotherapy with Vγ2Vδ2 T cells has few side effects but has resulted in only a few partial and complete remissions. Here, we have tested Vγ2Vδ2 T cells for expression of inhibitory receptors and determined whether adding PD-1 checkpoint blockade to adoptively transferred Vγ2Vδ2 T cells enhances immunity to human PC-3 prostate tumors in an NSG mouse model. We find that Vγ2Vδ2 T cells express PD-1, CTLA-4, LAG-3, and TIM-3 inhibitory receptors during the 14-day ex vivo expansion period, and PD-1, LAG-3, and TIM-3 upon subsequent stimulation by pamidronate-treated tumor cells. Expression of PD-L1 on PC-3 prostate cancer cells was increased by co-culture with activated Vγ2Vδ2 T cells. Importantly, anti-PD-1 mAb treatment enhanced Vγ2Vδ2 T cell immunity to PC-3 tumors in immunodeficient NSG mice, reducing tumor volume nearly to zero after 5 weeks. These results demonstrate that PD-1 checkpoint blockade can enhance the effectiveness of adoptive immunotherapy with human γδ T cells in treating prostate tumors in a preclinical model.Mohanad H. NadaHong WangAuter J. HusseinYoshimasa TanakaCraig T. MoritaTaylor & Francis Grouparticleadoptive immunotherapyprogramed cell death 1 receptorprostatic neoplasmsinhibitory t cell receptorscombined modality therapyhuman γδ t cellsvγ2vδ2 t cellsImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncoImmunology, Vol 10, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adoptive immunotherapy programed cell death 1 receptor prostatic neoplasms inhibitory t cell receptors combined modality therapy human γδ t cells vγ2vδ2 t cells Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	adoptive immunotherapy programed cell death 1 receptor prostatic neoplasms inhibitory t cell receptors combined modality therapy human γδ t cells vγ2vδ2 t cells Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Mohanad H. Nada Hong Wang Auter J. Hussein Yoshimasa Tanaka Craig T. Morita PD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer
description	Human Vγ2Vδ2 (also termed Vγ9Vδ2) T cells play important roles in microbial and tumor immunity by monitoring foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis. Accumulation of isoprenoid metabolites after bisphosphonate treatment allows Vγ2Vδ2 T cells to recognize and kill tumors independently of their MHC expression or burden of non-synonymous mutations. Clinical trials with more than 400 patients show that adoptive immunotherapy with Vγ2Vδ2 T cells has few side effects but has resulted in only a few partial and complete remissions. Here, we have tested Vγ2Vδ2 T cells for expression of inhibitory receptors and determined whether adding PD-1 checkpoint blockade to adoptively transferred Vγ2Vδ2 T cells enhances immunity to human PC-3 prostate tumors in an NSG mouse model. We find that Vγ2Vδ2 T cells express PD-1, CTLA-4, LAG-3, and TIM-3 inhibitory receptors during the 14-day ex vivo expansion period, and PD-1, LAG-3, and TIM-3 upon subsequent stimulation by pamidronate-treated tumor cells. Expression of PD-L1 on PC-3 prostate cancer cells was increased by co-culture with activated Vγ2Vδ2 T cells. Importantly, anti-PD-1 mAb treatment enhanced Vγ2Vδ2 T cell immunity to PC-3 tumors in immunodeficient NSG mice, reducing tumor volume nearly to zero after 5 weeks. These results demonstrate that PD-1 checkpoint blockade can enhance the effectiveness of adoptive immunotherapy with human γδ T cells in treating prostate tumors in a preclinical model.
format	article
author	Mohanad H. Nada Hong Wang Auter J. Hussein Yoshimasa Tanaka Craig T. Morita
author_facet	Mohanad H. Nada Hong Wang Auter J. Hussein Yoshimasa Tanaka Craig T. Morita
author_sort	Mohanad H. Nada
title	PD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer
title_short	PD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer
title_full	PD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer
title_fullStr	PD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer
title_full_unstemmed	PD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer
title_sort	pd-1 checkpoint blockade enhances adoptive immunotherapy by human vγ2vδ2 t cells against human prostate cancer
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/44888b298b5348eaa2d0982d33df0a10
work_keys_str_mv	AT mohanadhnada pd1checkpointblockadeenhancesadoptiveimmunotherapybyhumanvg2vd2tcellsagainsthumanprostatecancer AT hongwang pd1checkpointblockadeenhancesadoptiveimmunotherapybyhumanvg2vd2tcellsagainsthumanprostatecancer AT auterjhussein pd1checkpointblockadeenhancesadoptiveimmunotherapybyhumanvg2vd2tcellsagainsthumanprostatecancer AT yoshimasatanaka pd1checkpointblockadeenhancesadoptiveimmunotherapybyhumanvg2vd2tcellsagainsthumanprostatecancer AT craigtmorita pd1checkpointblockadeenhancesadoptiveimmunotherapybyhumanvg2vd2tcellsagainsthumanprostatecancer
_version_	1718444766311481344

PD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer

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